TMV in mouse lungs: more thoughts and refutations

I have been thinking about this paper (see last post), and it and other people’s posts (eg: Tommy Leung’s) have prompted more response.

I note the authors say the following:

“There is other published literature that challenges the dogma of the strict boundaries between plants and vertebrates for viruses. In non-vertebrate animals, it was shown that plant pathogenic viruses displayed complex interactions with insects, and the transcription and replication of some plant viruses within insects was described [29]–[32]. In addition, in some cases, insects were found to be affected by plant viruses [33]. Furthermore, it was recently shown that Tomato spotted wilt virus (TSWV) could infect two human cell lines, HeLa and diploid fibroblasts, depending on the expression of a viral polymerase-bound host factor[34]. Additionally, despite plant virus replication was not observed in animals, Cowpea mosaic virus (CPMV), a plant comovirus in the picornavirus superfamily, was able to bind and enter mammalian cells, including endothelial cells, and the binding protein for the virus was identified as a cell-surface form of the intermediate filament vimentin [35]. Furthermore, CPMV was found to persist for several days post oral or intravenous inoculation in a wide panel of body tissues in mice, including in the lung and the liver [36]. Additionally, it was demonstrated that TSWV induced a strong immune response in its insect vector Frankliniella occidentalis[37] and that oral administration of Cowpea severe mosaic virus, Alfalfa mosaic virus and chimeric plant virus particles induced a durable and systemic immune response in mice [38], [39]”

Yes. Um. Well. The “dogma of the strict boundaries between plants and vertebrates for viruses”? I have been teaching virology for 32 years, and I am not aware of actual DOGMA – as in, “that which has to be believed”. Rather, there has been the cumulative set of OBSERVATIONS that nothing that anyone has ever isolated out of a plant – and that replicates in it – has infected a vertebrate. I make that distinction, because there is always the possibility that, as we and others have found with insect viruses, plants can act as a “circulative, non-propagative vector” for insect viruses (for Rhopalosiphum padi aphid virus in barley, from my lab, and Leafhopper A virus in maize) – and if one realises that male mosquitoes, and often also females, feed on plants…you see where I’m going here? As in, it might well be possible for a virus that multiplies in an insect and also in a vertebrate, to POTENTIALLY be found in a plant?

In ay case, this is largely beside the point, because the authors get sidetracked into discussing Tomato spotted wilt – which happens to be a plant-adapted bunyavirus, most closely related to insect and vertebrate phleboviruses – “depending on the expression of a viral polymerase-bound host factor”. Really?? And if it isn’t there? Does the virus in fact spread? For that matter, my lab has cell-free translated two aphid picorna-like virus genomes in rabbit reticulocyte lysates, but we made no claim that it could happen in rabbit cells. Moreover, they make much of the fact that “a plant comovirus in the picornavirus superfamily, was able to bind and enter mammalian cells…[and] was found to persist for several days post oral or intravenous inoculation in a wide panel of body tissues in mice, including in the lung and the liver”.

Yes? And? A REALLY stable plant virus was able to bind and enter animal cells, and persist? The problem with that is…?

We in the virus-like particle vaccine field RELY on the fact that VLPs will be taken up by cells of the immune system in vertebrates, and that they will elicit immune responses – so why is this regarded as a problem? In fact, TMV has itself been tested as an RNA vaccine delivery system, due to its ability to protect a RNA payload, and get itself delivered into reticulocytes and macrophages – meaning this property has been known for some time, and has not hitherto been seen as a problem!

I think these authors have hyped something that is quite interesting into what THEY regard as a potential problem, for the purposes of getting their article accepted – and I think this needs to be recognised, and that the perceived risks need to be minimised by the knowledgeable.

3 Responses to “TMV in mouse lungs: more thoughts and refutations”

I found everyone’s comments fascinating and worthwhile. I’ve seen many “dogmas” overturned. Remember when we thought that the flow of genetic information was strictly from DNA to RNA? If it were not for the fact that HIV/AIDS is a horrific reality, it would have been considered a really stupid science fiction fantasy. And what about prions? Who would ever have guessed such a thing? And, viroids are pretty remarkable. It’s been my experience to keep an open mind about these things. Not to start any thing, but has anyone noticed that the filoviruses look more like TMV than anything else?

Oh, sure, I love the sound of a dogma yelping as it gets knocked to the kerb as much as the next atheist – and I have often wondered whether plant viruses CAN in fact infect mammalian cells, however transiently. There is all the work out of the Ahlquist lab on Brome mosaic virus and Flockhouse virus replication, where they have shown that both (very different) RNA viruses, infecting plants and insects respectively, can replicate in yeast (e.g.: http://www.ncbi.nlm.nih.gov/pubmed/21915247). However, this ONLY means they can REPLICATE – not infect them naturally.

The gulf between plants and mammals in terms of cofactors needed for RNA-dependent RNA polymerases, just to name one requirement for plant virus replication, is large enough that this means it is VERY unlikely to happen, or that it would constitute a viable infection if it did. Plant viruses do not enter plant cells by the same means that animal viruses enter animal cells: because of the existence and dimensions of plant cell walls, plant viruses enter cells either via transient damage to the cell wall and plasmalemma, or by direct injection by insect piercing mouthparts, or carriage in/on fungi or nematodes (http://www.mcb.uct.ac.za/tutorial/virusentplant.htm#b.%20%20%20%20Plant%20Cell%20Entry). Which means that spreading to the NEXT cell after replicating in one, would almost certainly be problematic.

So, not impossible – but like the Catholic Church suddenly allowing women to be priests, highly unlikely!